Skin penetration enhancers: Improving skin absorption

The skin is the largest organ of the human body. The outermost layer, called the stratum corneum, consists of dead cells which form a protective barrier to keep the bad stuff (germs & chemicals) out and the good stuff (water) in the body.

The structure of human skin

When we apply skincare products (or medicated gels/creams/ointments), we generally want the active ingredients to be able to penetrate the stratum corneum and enter into the deeper layers of the skin to exert their effect.

How do molecules cross the stratum corneum?

1.  Intercellular route – Molecules pass through the spaces between the dead cells. This is the predominant route.
2. Transcellular route – Molecules directly pass through the dead cells. This is the path of greatest resistance as the molecules need to penetrate the cell membranes and cell contents of the dead skin cells.
3.  Transappendageal route – Through sweat glands or hair follicles. Since sweat glands and hair follicles occupy only 0.1% of the total human skin surface, the contribution of this route is considered to be small (although it is still important).

How molecules may cross the stratum corneum

Why is it difficult for molecules to cross the stratum corneum?

As mentioned earlier, the predominant route of transport of molecules across the stratum corneum is via the intercellular route. But the spaces in between the dead skin cells are not just empty space; these spaces are filled with lipids (cholesterol, ceramide & free fatty acids) which form the lamellar lipid bilayer. These lipids contain hydrophilic (water-loving) head groups and lipophilic (greasy, oil-loving) chains. So, in order to cross the stratum corneum, molecules must be able to cross the lamellar lipid bilayer.

Structure of the lamellar lipid bilayer

What are skin penetration enhancers?

Skin penetration enhancers are compounds that are added into the formulation of a product to enhance the delivery of its active ingredients across the skin barrier.

How do skin penetration enhancers work?

These substances work through various mechanisms:

1.  By interacting with the hydrophilic head groups of the lipids in the lamellar lipid bilayer – this disrupts the packing order of the lipids, making it easier for active ingredient to diffuse through. (e.g. propylene glycol)
2.  By interacting with the greasy chains of the bilayer lipids. This also disrupts the packing order of the lipids. (e.g. oleic acid)
3. By hydrating the skin (e.g. urea)

What are some of the commonly used/studied skin penetration enhancers?

1.       Alcohols

a)      Short chain alcohols (e.g. ethanol, isopropyl alcohol)

b)      Long chain alcohols (e.g. octanol, nonanol, decanol, undecanol, lauryl alcohol, tridecanol, myristyl alcohol, oleyl alcohol, linoleyl alcohol, and linolenyl alcohol

2.       Fatty acid esters

-          Isopropyl myristate, ethyl oleate, glyceryl monolaurate, glyceryl mono-oleate, lauryl lactate, isopropyl palmitate, methyl oleate, oleyl oleate and sorbitan mono-oleate.

3.       Glycols

-          Propylene glycol

4.       Glycol ethers

-          Transcutol®

5.       Fatty acids

-          Oleic acid

6.       Sulphoxides

-          Dimethyl sulphoxide (seldom used due to skin irritating effects)

7.       Urea and derivatives

8.       Surfactants (e.g. Tween)

9.       Terpenes (found in essential oils)

References:

1.       Lane. Int J Pharm. 2013 Apr 15;447(1-2):12-21

2.       Trommer & Neubert. Skin Pharmacol Physiol. 2006;19(2):106-21